Delving into the Latest Updates on AGS-16C3F with Synapse

Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

Anti-ENPP3-MMAF

+ [1]

Target

ENPP3 x Tubulin

Mechanism

ENPP3 inhibitors(Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 inhibitors), Tubulin inhibitors

Therapeutic Areas

NeoplasmsUrogenital DiseasesOther Diseases

Active Indication-

Inactive Indication

Advanced Renal Cell CarcinomaMetastatic Renal Cell CarcinomaPapillary Renal Cell Carcinoma

Originator Organization

Agensys, Inc.

Active Organization-

Inactive Organization

Astellas Pharma Global Development, Inc.

Astellas Pharma, Inc.

Agensys, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

Structure

Molecular FormulaC39H65N5O8

InChIKeyMFRNYXJJRJQHNW-DEMKXPNLSA-N

CAS Registry745017-94-1

Boost your research with our XDC technology data.

login

or

view full example data

Boost your research with our XDC technology data.

Gene Sequence

Sequence Code 186372L

Sequence Code 186366H

AbstractTrial InformationClinicalTrials.gov Identifier: NCT02639182 Sponsor: Astellas Pharma, Inc. Principal Investigator: Christian Kollmannsberger IRB Approved: YesLessons LearnedThe primary endpoint of this phase II study that evaluated the efficacy and safety of the investigational compound, AGS-16C3F, versus axitinib in previously treated patients with metastatic renal cell carcinoma (mRCC) was not met. Median progression-free survival, the primary endpoint, was 2.9 months with AGS-16C3F and 5.7 months with axitinib (HR, 1.676; 95% CI, 1.107–2.537; p = .015), per investigator assessment The safety profile for each study drug was as expected, with the most commonly reported adverse events being fatigue (53%) and nausea (47%) in the AGS-16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm. These results provide a benchmark for axitinib use in heavily pretreated patients with mRCC.BackgroundAGS-16C3F is a novel antibody-drug conjugate that targets cell-surface ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) and is conjugated to a microtubule disruptive agent. Here we present findings from a phase II study of AGS-16C3F versus axitinib in metastatic renal cell carcinoma (mRCC).MethodsPatients with mRCC of any histology and disease progression during or after their last treatment regimen were randomized 1:1 to intravenous AGS-16C3F 1.8 mg/kg every 3 weeks or oral axitinib 5 mg twice daily (starting dose). The primary objective was investigator-assessed progression-free survival (PFS) of AGS-16C3F versus axitinib (RECIST version 1.1).ResultsIn the total population (N = 133), 63% (n = 84) of patients had completed the study at data cutoff (August 21, 2019). Median PFS was 2.9 months with AGS-16C3F and 5.7 months with axitinib (hazard ratio [HR], 1.676; 95% confidence interval [CI], 1.107–2.537; p = .015). There were no significant differences between arms in secondary efficacy endpoints, including overall survival (13.1 months, AGS-16C3F and 15.4 months, axitinib; HR, 1.079; 95% CI, 0.681–1.707; p = .747). In the safety population (n = 131), the most commonly reported adverse events were fatigue (53%) and nausea (47%) in the AGS-16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm. The incidence of diarrhea was lower in the AGS-16C3F arm than in the axitinib arm (17% vs. 48%), and ocular toxicities were more frequent in the AGS-16C3F arm than in the axitinib arm (44% vs. 26%).ConclusionThe investigational compound, AGS-16C3F, did not meet the primary endpoint of this trial. These study results provide a benchmark for axitinib use in heavily pretreated patients with mRCC.

26 Feb 2019·Blood Advances

In vitro and in vivo efficacy of an anti-CD203c conjugated antibody (AGS-16C3F) in mouse models of advanced systemic mastocytosis

Article

Author: Arock, Michel ; Baral, Viviane ; Zhang, Yanyan ; Louache, Fawzia ; Doñate, Fernando ; He, Liang ; Launay, Jean-Marie ; Wedeh, Ghaith ; Kouros-Mehr, Hosein ; Beghi, Florian ; Bibi, Siham ; Wittner, Monika

AbstractAntibody-drug conjugates (ADCs) are a new class of therapeutics that use antibodies to deliver potent cytotoxic drugs selectively to cancer cells. CD203c, an ecto-nucleotide pyrophosphatase-phosphodiesterase 3, is overexpressed on neoplastic mast cells (MCs) in systemic mastocytosis (SM), thus representing a promising target for antibody-mediated therapy. In this study, we have found that human neoplastic MC lines (ROSAKIT D816V and ROSAKIT D816V-Gluc), which express high levels of CD203c, are highly and specifically sensitive to the antiproliferative effects of an ADC against CD203c (AGS-16C3F). In these cell lines, AGS-16C3F induced cell apoptosis at very low concentrations. To characterize the effects of AGS-16C3F on leukemia progression in vivo, ROSAKIT D816V-Gluc NOD-SCID γ mouse models of advanced SM (AdvSM) were treated with AGS-16C3F or an ADC control for 2 weeks. Whereas AGS-16C3F had no apparent toxicity in xenotransplanted mice, in vivo neoplastic MC burden significantly decreased in both hematopoietic and nonhematopoietic organs. Furthermore, animals treated with AGS-16C3F had prolonged survival compared with the animals treated with control ADC, and AGS-16C3F efficiently prevented disease relapse. In conclusion, these preclinical studies identified CD203c as a novel therapeutic target on neoplastic MCs, and AGS-16C3F as a promising ADC for the treatment of patients with AdvSM.

15 Sep 2018·Clinical Cancer ResearchQ1 · MEDICINE

Phase I Trials of Anti-ENPP3 Antibody–Drug Conjugates in Advanced Refractory Renal Cell Carcinomas

Q1 · MEDICINE

Article

Author: Morrison, Karen ; Redman, Bruce G. ; Motzer, Robert J. ; Sangha, Randeep S. ; Doñate, Fernando ; Thompson, John A. ; Molina, Ana M. ; Ernst, D. Scott ; Heath, Elisabeth I. ; Choueiri, Toni K. ; Pili, Roberto ; Anand, Banmeet ; Trave, Fabio ; Kim, Stella K. ; Kollmannsberger, Christian K. ; Reyno, Leonard ; Wiseman, Aya

AbstractPurpose: To determine the safety, pharmacokinetics, and recommended phase II dose of an antibody–drug conjugate (ADC) targeting ectonucleotide phosphodiesterases-pyrophosphatase 3 (ENPP3) conjugated to monomethyl auristatin F (MMAF) in subjects with advanced metastatic renal cell carcinoma (mRCC).Patients and Methods: Two phase I studies were conducted sequentially with 2 ADCs considered equivalent, hybridoma-derived AGS-16M8F and Chinese hamster ovary–derived AGS-16C3F. AGS-16M8F was administered intravenously every 3 weeks at 5 dose levels ranging from 0.6 to 4.8 mg/kg until unacceptable toxicity or progression. The study was terminated before reaching the MTD. A second study with AGS-16C3F started with the AGS-16M8F bridging dose of 4.8 mg/kg given every 3 weeks.Results: The AGS-16M8F study (n = 26) closed before reaching the MTD. The median duration of treatment was 12 weeks (1.7–83 weeks). One subject had durable partial response (PR; 83 weeks) and 1 subject had prolonged stable disease (48 weeks). In the AGS-16C3F study (n = 34), the protocol-defined MTD was 3.6 mg/kg, but this was not tolerated in multiple doses. Reversible keratopathy was dose limiting and required multiple dose deescalations. The 1.8 mg/kg dose was determined to be safe and was associated with clinically relevant signs of antitumor response. Three of 13 subjects at 1.8 mg/kg had durable PRs (range, 100–143 weeks). Eight subjects at 2.7 mg/kg and 1.8 mg/kg had disease control >37 weeks (37.5–141 weeks).Conclusions: AGS-16C3F was tolerated and had durable antitumor activity at 1.8 mg/kg every 3 weeks. Clin Cancer Res; 24(18); 4399–406. ©2018 AACR.

100 Deals associated with AGS-16C3F

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Renal Cell Carcinoma	Phase 2	CA	Astellas Pharma Global Development, Inc.	03 May 2016
Metastatic Renal Cell Carcinoma	Phase 2	US	Astellas Pharma Global Development, Inc.	03 May 2016
Papillary Renal Cell Carcinoma	Phase 2	CA	Agensys, Inc.	18 Jul 2012
Papillary Renal Cell Carcinoma	Phase 2	US	Agensys, Inc.	18 Jul 2012
Advanced Renal Cell Carcinoma	Phase 2	US	Astellas Pharma, Inc.	01 Aug 2010

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02639182 (CTgov)	Phase 2	Metastatic Renal Cell Carcinoma	133	AGS-16C3F (AGS-16C3F)	kcvpkskdod(evbenuztkt) = eyqxabwdid vrqxxqajcn (cfcnlbttsm, pynphhhbsa - ldxlklrbuq) View more	-	23 Sep 2020
				Axitinib (Axitinib)	kcvpkskdod(evbenuztkt) = sjryndtmdj vrqxxqajcn (cfcnlbttsm, hmygyaqvij - kheqehtlaq) View more
NCT01114230 \| NCT01672775 (Pubmed \| Clin Cancer Res) Manual	Phase 1	Renal Cell Carcinoma	60	AGS-16M8F	(pzucwydqee) = giqsbumrnu gvxetapcxc (bhkjgnquwv ) View more	Positive	15 Sep 2018
				AGS-16C3F	(zzdvoftvgm) = kvsviexgls vmssteamjk (jcmrnnijbo ) View more